Understanding the effects of treatment with potent antiviral drugs is critical for epidemic control. Currently these drugs have successfully proven effective in prolonging the lives of patients infected with HIV, but they also have the unwanted effect of inducing drug-resistant strains of HIV that can cause the return of high viral burden within treated patients and thus not only render the drug ineffective, but also promote the dissemination of drug resistance throughout populations at risk. This grant application continues to address the statistical problems that arise in studying the development of resistant HIV. Specifically, we propose methods for: (1) modeling the relationship between HIV phenotype and genotype to enable the determination of patient phenotype on the basis of the less expensive and more quickly measured genotype; (2) modeling the evolution of genotype overtime in order to better control treatment strategies; (3) optimizing pooled designs to enable the early detection of acute HIV infection in an economically feasible way in order to better control the epidemic and promoting responsible behavior; (4) developing specimen pooling strategies for the surveillance of drug resistant HIV; and (5) spatio-temporal modeling of the spread of resistance at the population level, which together with (4) provides a unique method for this important task, especially in an economically challenged situation. These aims, if fulfilled, should help in the public health effort to control the spread of the epidemic and to better treat those already infected.